Blood Thinners

Blood-thinning agents are medications used to prevent blood clots from forming inside the human body in order to lower the risk of severely harmful conditions such as venous thromboembolism (VTE), pulmonary embolism (PE), and deep vein thrombosis (DVT). These drugs are vastly used all across the world for the prevention or treatment of other life-threatening conditions such as ischemic stroke, atrial fibrillation and myocardial. They’re also useful for the treatment of some acquired or genetic conditions such as hypercoagulability.

Are anticoagulants and antiplatelet medications the same thing as blood thinners?

Blood-thinning agents are grouped into two different categories: antiplatelet drugs, used to stop platelets from aggregating together and forming a clot (such as aspirin), and anticoagulants that increase the time required to form a blood clot (such as the inhibitors of factor Xa, heparins, and warfarin).

Anticoagulants

There are relatively few anticoagulant medications available and they’re both prescribed for long- and short-term therapies. For medium- or short-term treatment, the preferred anticoagulants are the injectable heparins, which act by inhibiting thrombin and factor Xa. The bind to the antithrombin III enzyme effectively preventing the formation of blood clots. There are several types of heparins, and all of them are biological substances. The most used ones are the Low-molecular-weight heparins since they do not require constant monitoring of the coagulation parameters. Other heparins need to be continuously controlled by monitoring a coagulation parameter called the activated partial thromboplastin time.

Dicumarol is the most known as well as the oldest anticoagulant. It is a Vitamin-K inhibitor that was discovered in 1930. Originally marketed as a poison for rats in 1948, dicumarol is now widely known as “Warfarin”. Its pharmaceutical properties were discovered by accident when a soldier who did not want to be enlisted for the Korean tried it for suicidal purposes. Doctors saved his life by administering a significant quantity of Vitamin K. A new warfarin-based medication named Coumadin was then approved by the FDA in 1954, to prevent the risk of stroke in several conditions. Warfarin is an antagonist of Vitamin-K that blocks the formation of the regulatory factors protein S, protein Z, and protein C and the activated forms of the Ca(2+)-dependent clotting factors II, VII, IX and X. This drug’s dosage must be continuously monitored to evaluate its anticoagulant properties. Parameters such as the international normalized ratio (INR) and the prothrombin ratio (PR) are frequently measured in appropriate clinics. Coumadin can, in fact, interact with Vitamin-K rich foods (broccoli, cabbage, kale, spinach), losing its effectiveness. On the other hand, if its blood levels are too high, it may have lethal consequences such as internal hemorrhages and bleedings, which can still be reversed by prompt administration of Vitamin K. These risks are even higher if this medicine is taken together with common over-the-counter painkillers including non-steroidal anti-inflammatory drugs (NSAIDs).

Antiplatelet agents

Antiplatelet agents are widely used for the long-term reduction of risk of thrombotic cardiovascular or cerebrovascular diseases in subjects who received a prosthetic heart implant, such as stent placement, angioplasty, and valve replacement. The mechanism of action is common for all antiplatelet drugs, although some differences can be noted. They all stop the aggregation of platelets, a group of blood cells that “clump together” forming a clot whenever a tissue or vessel is injured. The risk of potentially fatal bleeding during treatment with antiplatelet drugs is much lower that while under treatment with other anticoagulants. Whenever such life-threatening accidents happen, quick transfusion of fresh platelets can reverse the effects of these medications.

The oldest and most known antiplatelet drug is the aspirin, also called acetylsalicylic acid (ASA). Initially developed as a NSAID, scientists later discovered that a daily treatment with low doses of ASA can reduce the risk of strokes and heart attacks. Aspirin acts by irreversibly inhibiting the two isoforms of the cyclooxygenase enzyme (COX-1 and COX-2). The first one of these two enzymes is responsible for the production of an important prothrombotic substance: thromboxane (TX)A2. Aspirin can thus reduce the formation of thrombi.

Many other types of antiplatelet agents are currently marketed, and their mechanisms of actions are subtly different. Glycoprotein IIB/IIIA inhibitors (tirofiban, eptifibatide, abciximab), Phosphodiesterase inhibitors (cilostazol), Reversible P2Y12 Antagonists (elinogrel, ticagrelor, cangrelor), as well as many others. Probably, the most important of these groups is the Thienopyridines one (ticlopidine, prasugrel, clopidogrel). These medications act by inhibiting platelet function. The irreversibly modify the platelet P2Y12 receptor, blocking the adenosine diphosphate (ADP) function. Before its patent expired in 2010, Clopidogrel was the second most sold drug worldwide. Its sales grossed over USD $9 billion until Xarelto was approved in the US market rapidly taking its place.

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Novel Oral Anticoagulants (NOACs)

Novel Oral Anticoagulants (NOACs) are thethird group of blood thinners. A group of these agents acts by blocking the extrinsic and intrinsic pathways of the blood coagulation cascade by directly inhibiting the Factor Xa. These include edoxaban (Lixiana), apixaban (Eliquis) and rivaroxaban (Xarelto). Others such as argatroban and dabigatran (Pradaxa) act by directly inhibiting the enzyme thrombin (factor II) and are called direct thrombin inhibitors (DTI). Argatroban is only used to substitute some heparins if those medications caused thrombocytopenia. The last DTI, Ximelagatran, was recalled since it caused many cases of liver injury.

NOACs rapidly gained a huge popularity among doctors and patients since they do not need any monitoring or dietary restriction. However, these agents are the most dangerous among all other anticoagulants, since no antidote can reverse their effects. Xarelto and the other NOACs have been defined by many agencies as high-risk medicines that may severely harm a patient’s health. Doctors cannot save the life of a patient whenever a bleeding accident occurs, since neither the infusion with fresh platelets nor Vitamin K are effective. The Food and Drug Administration even reported that using these drugs is riskier than the administration of chemotherapic agents during cancer treatment.

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